In only 16,600 base pairs, human mitochondrial DNA (mtDNA) encodes 37 genes (2 for ribosomal RNAs, 22 for tRNAs and 13 for proteins) that are essential for cell viability. These genes are buffered against the effect of mutations, because somatic cells typically contain around 1000 copies of mtDNA. While most cells are apparently uniform with respect to mtDNA composition, mammalian cells can tolerate a significant fraction of aberrant mtDNA, a condition called heteroplasmy, and retain respiratory function. Nevertheless, mitochondria lack nucleotide excision and recombination repair systems, so that, with age, deletions and point mutations accumulate in mtDNA. This accretion of defects is thought to contribute to the infirmities of advanced age.
Significant obstacles remain to correcting any mtDNA in living animals since there is no delivery system for DNA into mitochondria. Therefore, a need exists in the art for the targeting and delivery of nucleic acids and other therapeutic molecules into the mitochondria.